Of Mice and Microbes....or the Grapes of Rats

Last week, an article published in The New England Journal of Medicine documented an outbreak of tularemia at a German vineyard in 2016. The outbreak occurred among grape harvesters at the vineyard, and a retrospective cohort study identified the likely source of infection as drinking “freshly pressed grape must”—newly pressed grapes (usually containing skin, stems, and seeds) that will be fermented to make wine—that had been contaminated with infected mice that were inadvertently pressed along with the grapes. This unusual, and disgusting, outbreak highlights the importance of tracing outbreaks to their source, particularly for unusual exposures, and its importance in preventing further spread of infection.

Tularemia

Tularemia, also known commonly as rabbit fever, is caused by the Francisella tularensis bacterium, and transmission can occur via tick or deer fly bites, skin contact with infected animals, ingestion of contaminated water, or inhalation of aerosols or contaminated dust particles. According to the US CDC, tularemia can take many forms. Symptoms typically include fever and swollen lymph nodes, but other manifestations often depend on how the bacteria entered the body. For example, tick or deer fly bites can result in skin ulcers (ulceroglandular), ocular exposure can manifest as inflamed or irritated eyes (oculoglandular), and inhalation can cause chest pain and difficulty breathing (pneumonic). In this outbreak, the victims likely ingested the bacteria, which can cause sore throat, mouth ulcers, and tonsillitis (oropharyngeal). Oropharyngeal tularemia can also present as upset stomach, diarrhea, and vomiting. Of course, this is also a common symptom of finding out that you drank squashed-up mouse guts in your wine.

Over the past several decades, the US has typically identified fewer than 200 cases of tularemia each year, although the most recent data show 314 and 230 cases for 2015 and 2016, respectively. In Europe, 592 cases were reported in 2014 (526 confirmed), with the majority of cases coming from Sweden (150), Hungary (140), and Spain (90). Based on epidemiological information included in 2007 WHO guidelines, tularemia is found almost exclusively in the Northern Hemisphere.

As an additional note, F. tularensis is classified as a Tier 1 Select Agent and a Category A bioterrorism threat agent by the US CDC due to its potential to be used as a biological weapon. Tularemia is not known to spread person to person; however, its symptoms can be incapacitating or potentially lethal, and the bacterium is highly infectious and can be transmitted via aerosols.

Investigation

F. tularensis infection is typically thought to spread via tick and deer fly bites or via consumption of contaminated water or animal meat. Presumably, this refers to the direct consumption of contaminated meat, so tracing the exposure to wine unknowingly contaminated by infected mice makes for an interesting outbreak investigation. The investigators were able to link all of the cases to a single vineyard in Germany, which harvested grapes both mechanically and by hand. All of the cases drank the grape must after harvesting grapes mechanically (6 of 8 individuals who drank the must became ill), compared to zero cases among those who did not. The mechanical harvesting equipment was later used at a different vineyard, but this was not associated with any additional cases of tularemia. The investigators identified F. tularensis DNA in wine pressed at the first vineyard, including cross-contamination in wine later pressed from grapes harvested by hand. Genetic sequencing also identified DNA from wood mice in the wine. The vintners confirmed that it is not uncommon to find rodents in mechanically harvested grapes, but the article does not discuss how vintners address this issue.

Conclusion

German health officials adeptly identified a cluster of tularemia cases and conducted a meticulous investigation to determine the unusual, and thoroughly disgusting, exposure to F. tularensis bacteria. Fortunately, the investigators were able to identify the source of the outbreak in time to confiscate and destroy all contaminated products before their sale to the public. Had health officials been content to stop the immediate spread of the disease and abandoned their investigation when no new cases were identified, they could have potentially allowed contaminated wine to make its way to consumers. It is unclear to what extent F. tularensis bacteria can survive in wine, but the outbreak could have been substantially larger, potentially spreading across the continent and around the world. At that point, it would have been very difficult to link the cases, ascertain a common exposure, and determine the source of the infection to prevent future cases.

Outbreak Observatory aims to collect information on challenges and solutions associated with outbreak response and share it broadly to allow others to learn from these experiences in order to improve global outbreak response capabilities.